Activation of D1 dopamine receptors stimulates the release of GABA in the basal ganglia of the rat.
ABSTRACT Here we have explored whether dopamine is able to modulate the release of gamma-aminobutyric acid (GABA) from striatal terminals to substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen. The type of dopamine receptors involved was assessed by the blocking effect of either SCH 23390 (D1 antagonist) or (-)-sulpiride (D2 antagonist) of the dopamine effect. Dopamine stimulated (EC50 3.2 microM) the depolarization-induced release of [3H]GABA from slices isolated from all of the above mentioned nuclei. SCH 23390 dose-dependently blocked the dopamine stimulation, but (-)-sulpiride did not show any blocking effect. The results suggest that dopamine via D1 receptors modulates the release of GABA from striatal GABAergic terminals.
- European Journal of Integrative Medicine 12/2009; 1(4):231-232. · 0.65 Impact Factor
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ABSTRACT: The National Research Council (NRC) has recently recognized the importance of developing integrated formulated product design tools. In response, it created the Committee on Integrated Computational Materials Engineering (CICME) which developed and published a road map for what it termed a Grand Challenge . In the report, the committee noted that in order to alleviate strain put on U.S. manufacturers from the swiftly changing and increasingly global marketplace, integrated design closely coupling computational models with manufacturing processes would be required. The term integrated' recognizes that the properties of products are controlled by a multitude of separate and often competing mechanisms that operate over a wide range of length and time scales. It is the linkage of the scales that remains the Grand Challenge' . In response to this call from CICME, the research community has shifted focus from developing only the physical form, function, and aesthetics of assembled products to the design of chemically formulated products . Chemically formulated products are products designed at the molecular level to deliver a specific desired attribute that may exist at multiples scales such as the quantum-, nano-, meso-, macro-, and mega-scales. Examples of formulated products include pharmaceuticals , proteins , organic semi-conductors , nano-structured materials  and many more product types. Using today's technology, designing these optimized molecules for a specific end-use has never more attainable. Recent achievements owe much of their successes to increased computational speeds and the advent of novel algorithms that improved the transfer of information between the formulated scales . One type of promising new algorithms utilize the reverse problem formulation which has been shown to significantly reduce the complexity and required computational time of product design problems. For example, Eden et. al.  demonstrated the ability of the reverse problem formulation to decouple product design problems from constitutive equations so that molecules can be designed prior to verification at the various scales, effectively reducing the computational complexity. Furthermore, Eljack et al.  extended the reverse problem formulation to include information from processes operating at the macro-scale. Additionally, Satyanarayana et al.  recently demonstrated the use of the reverse problem formulation combined with grid technology for polymer design with long range order approaching the meso-scale. While each of these applications of the reverse problem formulation has incorporated elements of multi-scale product design, the integration of the reverse problem formulation into the complete multi-scale framework has yet to be achieved. The main objective for this research is to extend the reverse problem formulation algorithm to include aspects of each of the length scales, thereby creating a framework where product synthesis, design, and optimization can be achieved with significantly reduced computational time. The research plan to achieve the objective entails the following: (1) the development of a centralized framework, (2) the development of an algorithm that chooses the appropriate properties to bridge each of the length scales, (3) the successful implementation of a property clustering algorithm to load the property descriptions into the framework. Independent validation steps will also be built in to the method and verified using published experimental results because of the profound importance of experimental results to calibrate and validate computational methods and fill gaps in the theoretical understanding . Due to the size of this project, proof-of-concept case studies will initially focus on experimentally derived parameters used in acetaminophen tablet design. A more robust case study exploring simulated parameters in polymer nano-composites may also be discussed, provided the expected results are achieved prior to the conference. References  Committee on Integrated Computational Materials Engineering, National Research Council (2008). Integrated Computational Materials Engineering: A Transformational Discipline for Improved Competitiveness and National Security. The National Academies Press, USA.  Hill, M. (2004) Product and Process Design for Structured Products. AIChE Journal, 50(8), pp. 1656-1661.  Solvason C.C., Chemmangattuvalappil N.G., Eden M.R. (2009) Decomposition Techniques for Multi-Scale Structured Product Design: Molecular Synthesis. Computer Aided Chemical Engineering (In Press).  Floudas C.A., Fung H.K., McAllister S.R., Monningmann, M., Rajgaria R. (2006) Advances in protein structure prediction and de novo protein design: A review. Chemical Engineering Science, 61(3), pp.966-988.  Farhang A.R and Deeter T. (1999) Theoretical characterization of phenylene-based oligomers, polymers, and dendrimers. Synthetic Metals, 100(1), pp. 141-162.  Fermeglia M. and Pricl S. (2009) Multiscale molecular modeling in nanostructured material design and process system engineering. Computers & Chemical Engineering (In Press).  Eden M.R., Jorgensen S.B., Gani R., and El-Halwagi M.M. (2003) Reverse problem formulation based techniques for process and product synthesis and design. Computer Aided Chemical Engineering, 15(1), pp. 451-456.  Eljack F.T., Eden M.R., Vasiliki K., Kazantzi Q., and El-Hawagi M.M. (2007) Simultaneous process and molecular design - A property based approach. AIChE Journal, 53(5), pp. 1232-1239.  Satyanarayana K.C., Abildskov J., and Gani, R. (2009) Computer-aided polymer design using group contribution plus property models. Computers & Chemical Engineering, 33, pp. 1004-1013.01/2010;
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ABSTRACT: In the present study, we found that PDE10A inhibitor papaverine, alone or in combination with the D1 receptor agonist SKF38393, did not change spontaneous IPSCs (sIPSCs) frequency or amplitude in the substantia nigra pars reticulata (SNpr). An increase in frequency, but not in amplitude, of sIPSCs was only observed when SKF38393 and PDE10A inhibitors were associated to perfusion with higher extracellular K(+). On the other hand, the amplitude of evoked IPSCs (eIPSCs) of the striato-nigral projection to SNpr, was increased in response to co-administration of SKF38393 and papaverine in normal extracellular potassium. Of note, both an increase in sIPSCs frequency and eIPSC amplitude could be obtained either by a robust stimulation of adenylyl cyclase (AC) with forskolin (10 μM) or by a lower dose of forskolin (1 μM) associated to PDE inhibition. We next investigated the effects produced by dopamine (DA) depletion in the striatum. Under this condition, SKF38393 alone increased either sIPSCs frequency and eIPSC amplitude. In addition, in the striatum of DA-depleted mice we found reduced PDE10A levels and higher cAMP-dependent phosphorylation in response to D1 receptor stimulation. In accordance with these biochemical data, perfusion with papaverine had no effect on the SKF38393-induced changes of IPSCs in slices of DA-depleted mice. These findings reveal a dynamic interplay between PDE10A activity, level of neuronal network depolarization and degree of dopaminergic tone in the ability of D1 receptors to facilitate the GABAergic transmission to SNpr neurons from the direct nigro-striatal pathway.Neuropharmacology 08/2013; · 4.82 Impact Factor